Abstract
The extracellular matrix has a crucial role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues; however, the underlying mechanisms remain elusive. By using Cre–Lox deletion we show that β1 integrins are required for normal mammary gland morphogenesis and lumen formation, both in vivo and in a three-dimensional primary culture model in which epithelial cells directly contact a basement membrane. Downstream of basement membrane β1 integrins, Rac1 is not involved; however, ILK is needed to polarize microtubule plus ends at the basolateral membrane and disrupting each of these components prevents lumen formation. The integrin–microtubule axis is necessary for the endocytic removal of apical proteins from the basement-membrane–cell interface and for internal Golgi positioning. We propose that this integrin signalling network controls the delivery of apical components to the correct surface and thereby governs the orientation of polarity and development of lumens.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Cell Culture Techniques
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Cell Polarity*
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Cells, Cultured
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Endocytosis
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Epithelial Cells / metabolism
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Epithelial Cells / physiology*
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Epithelial Cells / ultrastructure
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Extracellular Matrix / metabolism
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Female
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Gene Knockout Techniques
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Integrin beta1 / genetics
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Integrin beta1 / metabolism*
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Male
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Mammary Glands, Animal / cytology*
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Mammary Glands, Animal / growth & development
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Mice
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Mice, Inbred ICR
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Mice, Knockout
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Microtubules / metabolism*
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Microtubules / ultrastructure
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Morphogenesis
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Neuropeptides / metabolism
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Primary Cell Culture
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Protein Serine-Threonine Kinases / metabolism*
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Protein Transport
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Spheroids, Cellular / cytology
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Spheroids, Cellular / metabolism
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rac GTP-Binding Proteins / metabolism
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rac1 GTP-Binding Protein
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trans-Golgi Network / metabolism
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trans-Golgi Network / physiology
Substances
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Integrin beta1
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Neuropeptides
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Rac1 protein, mouse
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integrin-linked kinase
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Protein Serine-Threonine Kinases
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein